The broad objective of the proposed research is to investigate cellular interactions of thyroid molecules relevant to their effects on growth, development, and metabolism. We had previously suggested, and have provided experimental support for the concept that an amino acid function of the iodothyronines, namely their ability to be incorporated into proteins of developing organisms, may account for their effects on growth and differentiation. In the present proposal we are suggesting that the iodothyronines may function as precursor amino acids in the catecholamine biosynthetic pathway, leading to the development of metabolites which might influence overall energy transformations of the organism. Experiments designed to test this hypothesis include (1) studies of the metabolism of ring-labelled as well as iodine-labelled thyroxine following pharmacologic alteration of adrenergic nervous system activity; (2) autoradiographic studies of the distribution and localization of iodothyronines under condition of normal and altered adrenergic innervation; (3) in vitro studies of the effect of adrenergic enzymes and surviving adrenergic tissues on metabolism of iodothyronines, (4) preparation of hydroxylated, decarboxylated and methylated derivatives of the iodothyronines, analogous to those derived from tyrosine, in the pathway leading to the adrenergic neurotransmitter substances.